Giri Tusar, Maloney Susan E, Giri Saswat, Goo Young Ah, Song Jong Hee, Son Minsoo, Tycksen Eric, Conyers Sara B, Bice Annie, Ge Xia, Garbow Joel R, Quirk James D, Bauer Adam Q, Palanisamy Arvind
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Psychiatry, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA.
iScience. 2024 Jan 22;27(2):108960. doi: 10.1016/j.isci.2024.108960. eCollection 2024 Feb 16.
Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies.
尽管外源性催产素用于引产已有60年，但人们对其对发育中大脑的影响知之甚少。鉴于有争议的报告表明分娩期间使用催产素与自闭症谱系障碍（ASD）之间存在联系，我们采用了最近验证的大鼠催产素引产模型来解决这一重要问题。通过结合分子生物学、行为学和神经影像学分析，我们发现催产素引产会导致发育中大脑的催产素能信号发生性别特异性破坏，幼崽的沟通能力下降，共情样行为减少，尤其是在雄性后代中，并且功能性皮质连接存在广泛的性别依赖性变化。与我们的假设相反，ASD中通常受损的社交行为在很大程度上得以保留。总的来说，我们的基础研究为催产素引产对神经发育的影响提供了细致入微的见解，并为动物模型的机制研究和前瞻性纵向临床研究奠定了基础。
